The present invention relates to a novel hydrogen fluoride containing composition, application of the composition to a fluorination agent, and preparation process of a fluorine-containing compound by using the composition.
Many processes have so far been known on the halogenation reaction of an organic compound. Compounds which can be used for a halogenation agent include hydrogen halide, phosphorous halide, sulfur halide and halogen simple body. However, these compounds are very corrosive and toxic, and many of these compounds require special equipment and technique. Accordingly, the investigation for developing a halogenation agent has been still continued in view of handling, safety and reactivity.
The fluorination agents which have been conventionally used in fluorinating reactions include fluorine, anhydrous hydrogen fluoride and sulfur tetrafluoride. However, these conventional fluorination agents are difficult to handle because of toxicity, corrosivity and danger of explosion in reaction and thus special equipment and technique are required. It is also a problem that required selectivity of a fluorine bond in the reaction is poor. On the other hand, development of new products utilizing fluorine compounds has been carried out in various fields such as functional materials and physiologically active substances. Keeping pace with such trend, various fluorination agents are recently in a development stage.
Anhydrous hydrogen fluoride (HF) is widely used in a great amount as a basic fluorine source in the fluorine chemical industry. However, it is difficult to handle because of a low boiling point (b.p. 19.5xc2x0 C.) and strong toxicity and corrosivity. When using hydrogen fluoride, the equipment must have acid proof property and pressure tight structure. Further, specific technique is required, and thus it is very difficult to use in industry.
In order to solve these problems, a complex of HF and Lewis base has been developed as a fluorination agent which is easy to handle and exhibits reaction mechanism similar to hydrogen fluoride (hereinafter referred to as HF-like fluorination agent). For example, pyridine-70 wt % (HF)n (Olah agent) has been reported in J. Org. Chem., 44, 3872 (1979) and triethylamine-3HF has been described in Aldrichimica Acta., 28, 31 (1995). However, these fluorination agents are difficult to control in the preparation step due to a considerably exothermic reaction. Further, it is difficult to use in industry in view of recovery and reuse.
HF is an important fluorine source in the fluorine chemical industry. Consequently, the development of an improved HF-like fluorination agent is very significant in the area of fluorine chemistry in order to overcome handling problems and to make the application simple in broad area.
The subject of the present invention is to provide hydrogen fluoride, which is a suitable fluorination agent for the preparation of a fluorine- containing compound, in the form of a fluorination agent which is easy to handle and can be conveniently used.
As a result of an intensive investigation in order to solve these subjects, the present inventors have found that a hydrogen fluoride containing composition obtained by adding hydrogen fluoride to a compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more, preferably to the compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C., the composition is easy to handle and useful as a novel fluorination agent having fluorinating effect similar to hydrogen fluoride, and further found that the fluorinating reaction can progress in high safety with ease without requiring special equipment and technique. Thus the present invention has been completed.
That is, the aspect of the present invention is a hydrogen fluoride containing composition obtained by adding hydrogen fluoride to a compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more, preferably to the compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C., use of said composition for fluorination agent and a preparation process of a fluorine containing compound by using said composition for a fluorination agent.
The invention will be more specifically illustrated in items (1) to (7) below.
(1) A hydrogen fluoride containing composition comprising hydrogen fluoride and a compound being liquid in the standard state (25xc2x0 C., 1 atmosphere) and having a boiling point of 120xc2x0 C. or more, and a fluorination agent comprising said composition.
(2) A hydrogen fluoride containing composition comprising hydrogen fluoride and a compound being liquid in the standard state (25xc2x0 C., 1 atmosphere) and having a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C., and a fluorination agent comprising said composition.
(3) A hydrogen fluoride containing composition comprising 7 mol or more of hydrogen fluoride for 1 mol of a compound being liquid in the standard state (25xc2x0 C., 1 atmosphere) and having a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C., and a fluorination agent comprise said composition.
(4) A hydrogen fluoride containing composition and a fluorination agent comprising said composition in items (1) to (3) wherein (I) the compound is represented by the formula (1): 
wherein R1 to R4 are a substituted or unsubstituted alkyl or aryl group and can be the same or different, and R1 and R2 or R3 and R4 can bond to form a ring having a nitrogen atom or a nitrogen atom and other hetero atom, or R1 and R3 can bond to form a ring having a nitrogen atom or a nitrogen atom and other hetero atom, {circle around (2)} the compound is represented by the formula (6): 
wherein R7 and R8 are a substituted or unsubstituted alkyl or aryl group, R9 is a hydrogen atom or a substituted or unsubstituted alkyl or aryl group, these groups can be the same or different, and R7 and R9 can bond to form cyclic amide, {circle around (3)} the compound is represented by the formula (10):
R10xe2x80x94Oxe2x80x94R11xe2x80x83xe2x80x83(10)
wherein R10 and R11, are a substituted or unsubstituted alkyl or aryl group and can be the same or different, and R10 and R11, can bond to form cyclic ether, {circle around (4)} the compound is represented by the formula (12): 
wherein R12 and R13 are a substituted or unsubstituted alkyl or aryl group and can be the same or different, and R12 and R13, can bond to form cyclic ester or {circle around (5)} the compound has the formula (14): 
(5) A hydrogen fluoride containing composition and a fluorination agent comprising the composition wherein the compound represented by the formula (1) is: {circle around (6)} a compound represented by the formula (2): 
{circle around (7)} a compound represented by the formula (3): 
wherein a is an integer of 2 or 3, and R and R6 are a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms and can be the same or different, and the compound represented by the formula (3) is a compound having the formula (4): 
or the formula (5): 
and further {circle around (8)} the composition wherein the compound represented by the formula {circle around (6)} is a compound having the formula (7): 
the formula (8): 
or the formula (9): 
{circle around (9)} the composition wherein the compound represented by the formula (10) is a compound having the formula (11):
(CH3OCH2CH2)2Oxe2x80x83xe2x80x83(11)
or {circle around (10)} the composition wherein the compound represented by the formula (12) is a compound having the formula (13): 
As illustrated above, the invention is each composition above and the use of the composition for a fluorination agent.
(6) A preparation process comprising reacting the fluorination agent with a compound represented by the formula (15):
R14[C(X1)3]mxe2x80x83xe2x80x83(15)
wherein R14 is a substituted or unsubstituted alkyl, alkoxy, aryl or aryloxy group, X1 is a hydrogen, fluorine, chlorine, bromine or iodine atom and can be the same or different except three X, are not simultaneously hydrogen or fluorine atoms and three X1 do not consist of hydrogen and fluorine atoms alone, and m is an integer of 1 to 6, to obtain a fluorine compound represented by the formula (16):
R14[CFn(X2)3xe2x88x92n]mxe2x80x83xe2x80x83(16)
wherein R14 is a substituted or unsubstituted alkyl, alkoxy, aryl or aryloxy group, X2 is a hydrogen, chlorine, bromine or iodine atom and can be the same or different, and n is an integer of 1 to 3 and m is an integer of 1 to 6.
(7) A preparation process comprising reacting, as a compound represented by the formula (16), a heterocyclic aromatic compound represented by the formula (17):
R15[C(X1)3]mxe2x80x83xe2x80x83(17)
wherein R15 is a substituted or unsubstituted heterocyclic aromatic group, and X1 is a hydrogen, fluorine, chlorine, bromine or iodine atom and can be the same or different except three X1 are not simultaneously hydrogen or fluorine atoms and three X1 do not consist of hydrogen and fluorine atoms alone, and m is an integer of 1 to 9, to obtain a fluorine containing heterocyclic aromatic compound represented by the formula (18):
R15[CFn(X2)3xe2x88x92n]mxe2x80x83xe2x80x83(18)
wherein R15 is a substituted or unsubstituted heterocyclic aromatic group, and X2 is a hydrogen, chlorine, fluorine, bromine or iodine atom and can be the same or different, and n is an integer of 1 to 3 and m is an integer of 1 to 9.
In the preparation process, {circle around (1)} the heterocyclic aromatic compound represented by the formula (17) is cyclic compound having 1 to 4 elements of one or more species selected from the group consisting of nitrogen, oxygen and sulfur, for example, a heterocyclic aromatic compound having a ring selected from furan, thiophene, pyrrole, pyrazole, imidazole, isoxazole, thioazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, benzofuran, indole, thianaphthane, benzimidazole, benzoxazole, benzothiazole, benzotriazole, purine, quinoline, isoquinoline, cinnoline, quinoxaline, dibenzothiophene, acridine, and phenanthroline.
Further, {circle around (2)} the heterocyclic aromatic compound represented by the formula (17) is a compound represented by the formula (19): 
wherein R16 is a hydrogen atom or alkyl group having 1 to 4 carbon atoms, in particular, 4-chloro-3,5-bis(trichloromethyl)pyrozole having the formula (20): 
or, {circle around (3)} the heterocylic aromatic compound is a compound represented by the formula (21): 
wherein R17 and R18 are a hydrogen, chlorine or fluorine atom, a hydroxy, alkyl having 1 to 4 carbon atoms, alkoxy, aryl or aryloxy group and can be the same or different, in particular, 2,4-dichloro-5-trichloromethylpyridine having the formula (22): 
And further, {circle around (4)} the heterocyclic aromatic compound is a compound represented by the formula (23): 
wherein R19 and R20 are a hydrogen atom or an alkyl group having 1 to 4 carbon atoms and can be the same or different, and particularly is ethyl 1-methyl-3-trichloromethylpyrazole-4-carboxylate having the formula (24): 
The hydrogen fluoride containing composition of the invention can be used for a fluorination agent having a reaction mechanism similar to hydrogen fluoride.
Further, the composition agent can be used not only for a fluorination agent, but also for an acid catalyst. When using for a fluorination agent, the composition preferably contains 7 mole or more hydrogen fluoride for 1 mole of the above compound.
The fluorination agent can be recovered and reused with ease after finishing the reaction and thus provides increased economy.
The hydrogen fluoride containing composition of the invention is a composition comprising hydrogen fluoride and a below described compound.
That is, the compound is (a) liquid in the standard state (25xc2x0 C., 1 atmosphere) and is required to have (b) a boiling point of 120xc2x0 C. or more. More preferably, the compound is liquid in the standard state (25xc2x0 C., 1 atmosphere), has a boiling point of 120xc2x0 C. or more, and additionally has (c) pka of 12 or more at 25xc2x0 C.
Hydrogen fluoride which can be used is an anhydrous grade.
In the hydrogen fluoride containing composition of the invention, (i) the above compound and hydrogen fluoride can form salt or complex, (ii) Hydrogen fluoride can coordinate to a free electron pair in the compound molecule. (iii) Hydrogen fluoride can form straight or branched hydrogen bonding with partial inclusion of the compound molecule. Or (iv) Hydrogen fluoride can dissolve in the compound to form a simple mixture.
The properties of the compound which consist the hydrogen fluoride containing composition in the invention, that is, liquid state in the standard state (25xc2x0 C., 1 atmosphere), boiling point of 120xc2x0 C. or more and preferably pka of 12 or more at 25xc2x0 C., are specified in view of reaction temperature and reactivity when used for a fluorination agent.
The compounds constituting the hydrogen fluoride containing composition include various compounds having the above specified properties, preferably compounds selected from the group consisting of those represented by the formulas (1), (6), (10) and (12) and the formula (14) below.
A compound represented by the formula (1): 
wherein R1 to R4 are a substituted or unsubstituted alkyl or aryl group and can be the same or different, R1 and R2 or R3 and R4 can bond to form a ring having a nitrogen atom or a nitrogen atom and other hetero atom, and R1 and R3 can bond to form a ring having a nitrogen atom or a nitrogen atom and other hetero atom.
A compound represented by the formula (6): 
wherein R7 and R8 are a substituted or unsubstituted alkyl or aryl group, R9 is hydrogen atom, or a substituted or unsubstituted alkyl or aryl group and R7, R8 and R9 can be the same or different, and R7 and R9 can bond to form cyclic amide.
A compound represented by the formula (10):
R10xe2x80x94Oxe2x80x94R11xe2x80x83xe2x80x83(10)
wherein R10 and R11 are a substituted or unsubstituted alkyl or aryl group and can be the same or different, and R10 and R11 can bond to form a cyclic ether.
A compound represented by the formula (12): 
wherein R12 and R13 are a substituted or unsubstituted alkyl or aryl group and can be the same or different, and R12 and R13 can bond to form a cyclic ester.
A compound having the formula (14): 
Each compound will be illustrated herein after.
(i) In the compound represented by the formula (1), R1 to R4 are a substituted or unsubstituted alkyl or aryl group, preferably alkyl or aryl group having 1 to 6 carbon atoms and can be the same or different, and the alkyl group having can be straight or branched.
The alkyl and aryl groups include, for example, a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, n-hexyl, cyclohexyl and phenyl group.
Further, R1 and R2 or R3 and R4 can respectively bond to form a heterocyclic ring having a nitrogen atom and 3 to 5 carbon atoms, which includes, for example, a pyrrolidine ring and piperidine ring.
Moreover, R1 and R3 can bond to form a heterocyclic, 5 or 6 membered ring having two nitrogen atoms as represented by the formula (3): 
Such a ring includes, for example, an imidazolidinone ring and pyrimidinone ring.
Specific compounds which can be represented by the formula (1) and formula (3) include, for example, 1,1,3,3-tetramethylurea, 1,3-dimethyl-2-imidazolidinone, 1,3-diethylimidazolidinone, 1,3-di(n-propyl)-2-imidazolidinone, 1,3-di(n-butyl)-2-imidazolidinone, N,Nxe2x80x2-dimethylpropyleneurea, N,Nxe2x80x2-diethylpropyleneurea, N,Nxe2x80x2-di(n-propyl)propyleneurea and N,Nxe2x80x2-di(n-butyl)propyleneurea.
The compounds represented by the formula (1) is preferably 1,1,3,3-tetramethylurea having the formula (2) 
In the compounds represented by the formula (3): 
R5 and R6 are a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms and can be the same or different, and include, for example, a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, n-hexyl and cyclohexyl group.
The compound represented by the formula (3) is preferably 1,3-dimethyl-2-imidazolidinone having the formula (4): 
or N,Nxe2x80x2-dimethylpropyleneurea having the formula (5): 
Particularly preferred compound represented by the formula (1) is 1,3-dimethyl-2-imidazolidinone.
(ii) In the compounds represented by the formula (6): 
R7 and R8 are a substituted or unsubstituted alkyl or aryl group, R9 is a hydrogen atom or a substituted alkyl or aryl group, and R7, R8 and R9 can be the same or different. The alkyl or aryl group includes, for example, a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, n-hexyl, cyclohexyl and phenyl group. R7 and R9 can bond to form cyclic amide.
N,N-diethylformamide, N,N-dimethylacetoamide having the formula (8): 
and 1-methyl-2-pyrrolidone having the formula (9): 
(iii) In the compound represented by the formula (10):
R10xe2x80x94Oxe2x80x94R11xe2x80x83xe2x80x83(10)
R10 and R11 are a substituted or unsubstituted alkyl, alkoxyalkyl or aryl group and can be the same or different. R10 and R11 include, for example, an alkyl group having more than 4 carbon atoms or phenyl group, and can bond to form cyclic ether having 1 to 3 oxygen atoms.
Specific compounds represented by the formula (10) include n-butyl ether, n-hexyl ether, anisole, phenetole, butyl phenyl ether, amyl phenyl ether, methoxytoluene, benzyl ethyl ether, diphenyl ether, dibenzyl ether, 1,2-diethoxyethane, 1,2-dibutoxyethane, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, and diethylene glycol dibutyl ether, preferably, diethylene glycol dimethyl ether having the formula (11):
(CH3OCH2CH2)2Oxe2x80x83xe2x80x83(11)
(iv) In the compound represented by the formula (12): 
R12 and R13 are a substituted or unsubstituted alkyl or aryl group and can be the same or different. Representative alkyl or aryl groups include, for example, a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, npentyl, n-hexyl, cyclohexyl, and phenyl group.
R12 and R13 can bond to form cyclic ester.
Specific compounds represented by the formula (12) include n-butyl acetate, n-pentyl acetate, isopentyl acetate, cyclohexyl acetate, benzyl acetate, butyl propionate, isopentyl propionate, methyl benzoate, dimethyl phthalate, and xcex3-butyrolactone, preferably n-butyl acetate having the formula (13): 
(v) The compound having the formula (14) is hexamethylphosphoramide.
As to the hydrogen fluoride containing composition of the invention, hydrogen fluoride is preferably in such an amount that the composition does not release hydrogen fluoride out of the system in the standard state (25xc2x0 C., 1 atmosphere). The amount of hydrogen fluoride depends upon species, property and temperature of the compound which constitutes the hydrogen fluoride containing composition. The molar number of hydrogen fluoride per mole of the compound which constitutes the hydrogen fluoride containing composition is generally 2 to 25 moles, preferably 7 to 20 moles, more preferably 10 to 18 moles.
When the compound constituting the hydrogen fluoride containing composition forms salt or complex with hydrogen fluoride, it is liable to form a mixture of salt or complex which differs in the coordination number, for example, 1 HF salt or 2 HF salt of the compound. The term xe2x80x9cthe molar number of hydrogen fluoride per mole of the hydrogen fluoride containing compositionxe2x80x9d is referred to as the value obtained by dividing the molar number of the total hydrogen fluoride with the molar number of the compound, and is defined to indicate the average molar number of hydrogen fluoride for 1 mole of the compound which constitutes the hydrogen fluoride containing composition.
The hydrogen fluoride containing composition can be prepared by adding anhydrous hydrogen fluoride to the compound for constituting the hydrogen fluoride containing composition.
Anhydrous hydrogen fluoride can be added in the liquid state or can be blown through the compound in the gaseous state.
Anhydrous hydrogen fluoride is added at temperature of xe2x88x9220 to 20xc2x0 C., preferably xe2x88x9210 to 10xc2x0 C., more preferably, 0 to 5xc2x0 C.
Anhydrous hydrogen fluoride can be added at velocity which inhibits short pass of anhydrous hydrogen fluoride and does not accompany violent exotherm. For example, when the amount of anhydrous hydrogen fluoride to be added is approximately 100 g for 50 g of the compound, the addition velocity is usually 1.5 to 3.0 g/min,, preferably 2.0 to 2.5 g/min. However, at the initiation time of anhydrous hydrogen fluoride addition, exotherm becomes great and thus slow down of the addition velocity is sometimes required.
The hydrogen fluoride containing composition of the invention is stirred at desired temperature after blowing anhydrous hydrogen fluoride, excessive hydrogen fluoride is released out of the reaction system to bring hydrogen fluoride content into equibilium state, and thus hydrogen content can be controlled to a desired level.
The hydrogen fluoride containing composition of the invention can be stored preferably in a hydrogen fluoride resistant container, more preferably, in a hydrogen fluoride resistant pressure vessel, and can be used for a fluorination agent or catalyst of various reactions.
The present invention uses the above hydrogen fluoride containing composition for a fluorination agent.
The fluorination agent of the invention respectively corresponds to the above hydrogen fluoride containing composition, that is, for example:
(1) A fluorination agent comprising hydrogen fluoride and a compound which is liquid in the standard state(25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more.
(2) A fluorination agent comprising hydrogen fluoride and a compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C.
(3) A fluorination agent comprising hydrogen fluoride and a compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C., and having a hydrogen fluoride molar number of 7 or more for 1 mole of the compound.
Similarly, the hydrogen fluoride containing composition having other embodiment of the invention is respectively defined as a fluorination agent.
In the invention, on the basis of the molar ratio of hydrogen fluoride to the compound which constitutes the hydrogen fluoride containing composition, the fluorination agent is indicated, for example, by DMI.nHF when the compound is 1,3-dimethylimidazolidinone (DMI).
The fluorination agent of the invention can be applied not only to the reaction wherein hydrogen fluoride is effective as a fluorination agent, but to other various fluorinating reactions, and is useful for fluorination of a fluoro-organic compound, particularly for a fluorination agent in the fluorinating reaction illustrated below.
The reaction is a preparation process of a fluorine containing compound by way of a halogen exchange reaction using the halogenation agent of the invention, that is, a halogen exchange reaction of a halogen containing aliphatic, aromatic or heterocyclic aromatic compound.
That is, a halogenide represented by the formula (15):
R14[C(X1)3]mxe2x80x83xe2x80x83(15)
wherein R14, is a substituted or unsubstituted alkyl, alkoxy, aryl or aryloxy group, and X1 is a hydrogen, fluorine, chlorine, bromine or iodine atom and can be the same or different except three X1 are not simultaneously hydrogen or fluorine atoms and three X1 do not consist of hydrogen and fluorine atoms alone, and m is an integer of 1 to 6, is reacted with the hydrogenation agent of the invention to prepare a fluorine compound represented by the formula (16):
R14[CFn(X2)3xe2x88x92n]mxe2x80x83xe2x80x83(16)
wherein R14, is a substituted or unsubstituted alkyl, alkoxy, aryl or aryloxy , group, and X2 is a hydrogen, chlorine, bromine or iodine atom and can be the same or different, and n is an integer of 1 to 3 and m is an integer of 1 to 6.
Representative compounds represented by the formula (15) includes, for example, 1,1,1,3-tetrachloro-3-methylbutane, benzyl chloride, benzoyl chloride, benzotrichloride, (chlorodifluoromethyl)benzene, (dichlorofluoromethyl)benzene, 2-chlorobenzotrichloride, 4-chlorobenzotrichloride, dichlorobenzotrichloride, 2-fluorobenzotrichloride, 2-nitrobenzotrichloride, 3-nitrobenzotrichloride, 4-nitrobenzotrichloride, (trichloromethyl)benzene, 1,3-bis(trichloromethyl)benzene and 1,4-bis(trichloromethyl)benzene. However, these compounds do not limit the scope of the invention.
These compounds represented by the formula (15) can be respectively converted to the corresponding fluorine compounds represented by the formula (16).
A halogenated heterocyclic aromatic compounds represented by the formula (17):
R15[C(X1)3]mxe2x80x83xe2x80x83(17)
wherein R15, is a substituted or unsubstituted heterocyclic aromatic group, and X1 is a hydrogen, fluorine, chlorine, bromine or iodine atom and can be the same or different except three X1 are not simultaneously a hydrogen or fluorine atom and three X1 do not consist of a hydrogen or fluorine atom alone, and m is an integer of 1 to 9, reacts with the fluorination agent of the invention to prepare a fluorine containing heterocyclic aromatic compound represented by the formula (18):
R15[CFn(X2)3xe2x88x92n]mxe2x80x83xe2x80x83(18)
wherein R15, is a substituted or unsubstituted heterocyclic aromatic group, and X2 is a hydrogen, chlorine, chlorine, bromine or iodine atom and can be the same or different, and n is an integer 1 to 3 and m is an integer of 1 to 9.
The term xe2x80x9cheterocyclic aromatic compoundxe2x80x9d in the invention is referred to as a heterocyclic compound having 1 to 4 atoms of one or more species of element selected from the group consisting of nitrogen, oxygen and sulfur.
In the formulas (17) and (18), m is an integer of 1 to 9 and is the number of trihalomethyl group located as a side chain.
The number of configuration is restricted due to the structure of a common heterocyclic compound and thus the upper limit is appropriately 9.
Generally, the velocity of a halogen exchange reaction is liable to reduce with increase in the number of m.
The heterocyclic aromatic compounds represented by the formula (17) preferably have a ring selected from furan, thiophene, pyrrole, pyrazole, imidazole, isoxazole, thiazole, thiodiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, benzofuran, indole, thionaphthene, benzimidazole, benzoxazole, benzothiazole, benzotriazole, purine, quinoline, isoquinoline, cinnoline, quinoxaline, dibenzothiophene, acridine and phenanthroline.
The compounds represented by the formula (17) will be exemplified below. However, these compounds are not to be construed to limit the scope of the invention.
Exemplary compounds are as follows.
Oxygen containing heterocyclic aromatic compounds include 3-trichloromethylfuran, 3-tribromomethylfuran, 2,3-bis(trichloromethyl)benzofuran and 2,3-bis(tribromomethyl)benzofuran.
Sulfur containing heterocyclic aromatic compounds include 2-trichloromethylthiophene, 3-trichloromethylthiophene, 2,3-bis(trichloromethyl)thiophene, 2,5-bis(trichloromethyl)thiophene, 3,4-bis(trichloromethyl)thiophene, 2-tribromomethylthiophene, 3-triboromomethylthiophene, 2,3-bis(tribromomethyl)thiophene, 2,5-bis(tribromomethyl)thiophene, 3,4-bis(tribromomethyl)thiophene, 2-trichloromethylthionaphthene, 2-trichloromethylthionaphthene, 4,6-bis(trichloromethyl)dibenzothiophene and 4,6-bis(tribromomethyl)dibenzothiophene.
Nitrogen containing heterocyclic aromatic compounds include 2-trichloromethylpyrrole, 2-tribromomethylpyrrole, 4-chloro-3-trichloromethylpyrazole, 4-chloro-3,5-bis(trichloromethyl)pyrazole, 4-chloro-3-tribromomethylpyrazole, 4-chloro-3,5-bis(tribromomethyl)pyrazole, 1-methyl-3-trichloromethylpyrazole-4-carboxylate, 1,2-bis(trichloromethyl)imidazole, 1,3-bis(trichloromethyl)imidazole, 1,5-bis(trichloromethyl)imidazole, 2,5-bis(trichloromethyl)imidazole, 4,5-bis(trichloromethyl)imidazole, 1,2,5-tris(trichloromethyl)imidazole, 2,3,4-tris(trichloromethyl)imidazole, 1,2-bis(tribromomethyl)lmidazole, 1,3-bis(tribromomethyl)imidazole, 1,5-bis(tribromomethyl)imidazole, 2,5-bis(tribromomethyl)imidazole, 4,5-bis(tribromomethyl)imidazole, 1,2,5-tris(tribromomethyl)imidazole, 2,3,4-tris(tribromomethyl)imidazole, 2-trichloromethylpyridine, 3-trichloromethylpyridine, 4-trichloromethylpyridine, 2,3-2,5-bis(trichloromethyl)pyridine, 2,6-bis (trichloromethyl)pyridine, 3,5-bis(trichloromethyl)pyridine, 2-tribromomethylpyridine, 3-tribromomethylpyridine, 4-tribromomethylpyridine, 2,3-2,5-bis(tribromomethyl)pyridine, 2,6-bis(tribromomethyl)pyridine, 3,5-bis(tribromomethyl)pyridine, 3-trichloromethylpyridazine, 3-tribromomethylpyridazine, 4-trichloromethylpyridazine, 4-tribromomethylpyridazine, 2,4-bis(trichloromethyl)pyrimidine, 2,6-bis(trichloromethyl)pyrimidine, 2,4-bis,(tribromomethyl)pyrimidine, 2,6-bis(tribromomethyl)pyrimidine, 2,4-dichloro-5-trichloromethylpyridine, 2-trichloromethylpyrazine, 2-tribromomethylpyrazine, 1,3,5-trisbis(trichloromethyl)triazine, 1,3,5-trisbis(tribromomethyl)triazine, 4-trichloromethylindole, 5-trichloromethylindole, 4-tribromomethylindole, 5-tribromomethylindole, 2-trichloromethylbenzimidazole, 2-tribromomethylbenzimidazole, 5-trichloromethyl-1H-benzotriazole, 5-tribromomethyl-1H-benzotriazole, 6-trichloromethylpurine, 6-tribromomethylpurine, 3-trichloromethylquinoline, 4-trichloromethylquinoline, 3-tribromethylquinoline, 4-tribromomethylquinoline, 3-trichloromethylisoquinoline, 3-tribromomethylisoquinoline, 4-trichloromethylcinnoline, 4-tribromomethylcinnoline, 2-trichloromethylquinoxaline, 2-tribromomethylquinoxaline, 5-trichloromethylquinoxaline, 5-tribromomethylquinoxaline, 9-trichloromethylacridine, 9-tribromomethylacridine, 4-trichloromethyl-1,10-phenanthroline, 4-tribromomethyl-1,10-phenanthroline, 5-trichloromethyl-1,10-phenanthroline, and 5-tribromomethyl-1,10-phenanthroline.
Oxygen and nitrogen containing heterocyclic aromatic compounds include 3,5-bis(trichloromethyl)isoxazole, 3,5-bis(tribromomethyl)isoxazole, 2-trichloromethylbenzoxazole, and 2-tribromomethylbenzoxazole.
Sulfur and nitrogen containing heterocyclic aromatic compounds include 4,5-bis(trichloromethyl)thiazole, 4,5-bis(tribromomethyl)thiazole, 5-trichloromethylthiodiazole, 5-tribromomethylthiodi azole, 2-trichloromethylbenzothiazole, and 2-tribromomethylbenzothiazole.
Compounds which can be favorably fluorinated in particular are those represented by the formula (19): 
wherein R16 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, for example, 4-chloro-3,5-bis(trichloromethyl)pyrazole having the formula (20): 
by the formula (21): 
wherein R17 and R18 are a hydrogen, chlorine or fluorine atom or a hydroxyl, alkyl or alkoxy group having 1 to 4 carbon atoms, aryl or aryloxy group, and can be the same or different, for example, 2,4-dichloro-5-trichloromethylpyrimidine having the formula (22): 
and further by the formula (23): 
wherein R19 and R20 are a hydrogen atom or alkyl group having 1 to 4 carbon atoms and can be the same or different, for example, ethyl 1-methyl-3-trichloromethylpyrazole-4-carboxylate having the formula (24): 
As illustrated above, these compounds represented by the formula (17) can be respectively converted to the corresponding flourine compounds represented by the formula (18).
The fluorination agent is used in an amount containing usually 1 equivalent or more, preferably 2 to 10 equivalents of hydrogen fluoride for 1 halogen atom to be substituted.
When a solvent is used for the reaction, no particular restriction is imposed upon the solvent as long as the solvent does not form complex by interaction with hydrogen fluoride. Preferred solvent includes acetonitrile, dichloromethane and ethylene dichloride.
The reaction temperature depends upon the solvent and reactivity of substrate, and is in the range of preferably xe2x88x9240 to 160xc2x0 C., were preferably xe2x88x9220 to 150xc2x0 C. in view of reaction velocity and stability of the fluorination agent.
The halogen exchange reaction of the compounds represented by the formulas (15) and (17) is a consecutive reaction.
The number of fluorine to be introduced can be controlled to 1 to 3 by adjusting the reaction temperature, pressure and hydrogen fluoride content of the fluorination agent.
In the fluorination reaction of the invention, the fluorination agent is formed by addition of hydrogen fluoride to the compound for constituting the hydrogen fluoride containing composition of the invention. Successively, a compound to be reacted can be added to the resulting fluorination agent and the fluorine exchange reaction can be carried out. That is, the composition can be formed by adding hydrogen fluoride to the compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more, or to the compound which is liquid in the standard state (25xc2x0 C., 1 atmosphere) and has a boiling point of 120xc2x0 C. or more and pka of 12 or more at 25xc2x0 C., the compound to be fluorinated is charged to the resulting composition, and the fluorination reaction can be carried out.
In the reaction, anhydrous hydrogen fluoride is usually added in such a velocity that short pass of anhydrous hydrogen fluoride does not occur and violent exotherm is not accompanied.
For example, when the addition amount of anhydrous hydrogen fluoride is appropriately 100 g for 50 g of the compound which constitutes the hydrogen fluoride containing composition, the addition velocity is usually 1.5 to 3.0 g/min, preferably 2.0 to 2.5 g/min. However, exotherm is great at the initiation time of anhydrous hydrogen fluoride addition and thus slow down of addition velocity is required.
The addition temperature of anhydrous hydrogen fluoride depends upon the reactivity of the solvent and reaction substrate and is in the range of preferably xe2x88x9240 to 100xc2x0 C., more preferably xe2x88x9220 to 90xc2x0 C. in view of the reaction velocity of a successive fluorinating reaction and stability of the fluorination agent.
The fluorine compound formed by the fluorinating reaction using the fluorination agent of the invention can be isolated with ease from the reaction mixture by way of extraction, recrystallization or distillation.
After the reaction, the fluorination agent can be recovered consumed amount of hydrogen fluoride is supplemented to the recovered fluorination agent, and the resulting reactivated agent can be used again.